Prosthetic implants such as meshes, combination mesh products or other porous prostheses are commonly used to provide a physical barrier between types of tissue or extra strength to a physical defect in soft tissue. However, such devices are often associated with post-surgical complications including post-implant infection, pain, excessive scar tissue formation and shrinkage of the prosthesis or mesh. Excessive scar tissue formation, limited patient mobility, and chronic pain are often attributed to the size, shape, and mass of the implant and a variety of efforts have been undertaken to reduce the amount of scar tissue formation. For example, lighter meshes using smaller fibers, larger weaves, and/or larger pore sizes as well as meshes woven from both non-resorbable and resorbable materials are in use to address these concerns.
For treating acute pain and infection, patients with implanted prostheses are typically treated post-operatively with systemic antibiotics and pain medications. Patients will occasionally be given systemic antibiotics prophylactically; however, literature review of clinical trials does not indicate that systemic antibiotics are effective at preventing implant-related infections.
In 1992, it was reported that nosocomial infections involved over 2 million patients each year and cost the healthcare systems over 4.5 billion dollars annually.1 Today, these numbers are undoubtedly much higher. Surgical site infections, involving approximately 500,000 patients, represent the second most common cause of nosocomial infections and approximately 17% of all hospital-acquired infections.2 The incidence of infections associated with the placement of pacemakers has been reported as 0.13 to 19.9% at an average cost of $35,000 to treat these complications which most often involves complete removal of the implant.3,4 
Post-operative infection is tied to a number of different elements: lack of host defense mechanisms, the clinical site where the surgery is performed, the length of the surgery, and bacteria present at the time of device implantation.5 The general health of the patient (i.e., the host factor) is always important; however, since many patients requiring surgery are compromised in some way—and there is little that can be done to mitigate that factor—controlling the other two factors becomes important.
Studies have shown that patients are exposed to bacterial contamination in the hospital, especially in the operating room (OR) and along the route to the OR.6 In fact, bacterial counts of up to 7.0×104 CFU/mL2 have been found in the OR dressing area.6 In addition, many surgical procedures are not performed in a “formal” OR, but rather are performed in a day-surgery or out-patient surgical center (e.g., procedures such as changing batteries in medical devices are not necessarily carried out in an OR). Recent improvements in air handling and surface cleansing have reduced the environmental levels of infectious agents, but not eliminated them. Consequently, further means to reduce bacterial contamination or to reduce the potential for bacterial infection are desirable.
Controlling the inoculation levels is the third component to the intra- and post-operative surgical infection control triad. One aspect to microbial control is the use antibiotics. For example, one practice advocates the administration of systemic antibiotics within 60 minutes prior to incision, with additional dosing if the surgery exceeds 3 hours.5 Such pre-incision administration has shown some positive effects on the incidence of infection associated with the placement of pacemakers.7 Surgeons also routinely wash the surgical site with an antimicrobial agent such as an Iodophor or antibiotic or a combination of agents. None of these procedures have been standardized nor have they been found to be efficacious. An adjunctive approach to managing the potential for implant contamination has been the introduction of antimicrobial agents on implantable medical devices.8,9 
This approach was initially developed to create a barrier to microbial entry into the body via surface-penetrating devices, such as indwelling catheters,9-11 The antimicrobial agents were applied in solution as a direct coating on the device to prevent or reduce bacterial colonization of the device and, therefore, reduce the potential for a device-related infection. While a number of clinical trials have demonstrated that antimicrobial coating on devices, such as central venous catheters reduce device colonization, reduction of infection has not been statistically significant although the numerical trends show a reduction in patient infection.12-18 These results are highly relevant since they tend to establish that, with proper aseptic and surgical techniques as well as administration of appropriate antibiotic therapy, the use of surface-modified devices has a positive impact on the overall procedural/patient outcome.12,13 
The development of post-operative infection is dependent on many factors, and it is not clear exactly how many colony forming units (CFUs) are required to produce clinical infection. It has been reported that an inoculation of 103 bacteria at the surgical site produces a wound infection rate of 20%.5 And while current air-handling technology and infection-control procedures have undoubtedly reduced the microbial levels in the hospital setting, microbial contamination of an implantable device is still possible. It is known that bacteria, such as Staphylococcus can produce bacteremia within a short time after implantation (i.e., within 90 days) with a device or lay dormant for months before producing an active infection so eradication of the bacterial inoculum at the time of implantation is key and may help to reduce late-stage as well as early-stage device-related infections.22 
For example, the combination of rifampin and minocycline has demonstrated antimicrobial effectiveness as a coating for catheters and other implanted devices, including use of those drugs in a non-resorbable coating such as silicone and polyurethane.13, 19-21 The combination of rifampin and minocycline has also been shown to reduce the incidence of clinical infection when used as a prophylactic coating on penile implants.
U.S. Ser. No. 11/672,929 describes a bioresorbable polymer coating on a surgical mesh as a carrier for the antimicrobial agents rifampin and minocycline. Such meshes can be fashioned into a pouch of various sizes and shapes to match the implanted pacemakers, pulse generators, defibrillators and other implantable medical devices. The addition of the antimicrobial agents permits the pouch to deliver antimicrobial agents at the implant site and thus to provide a barrier to microbial colonization of a CRM during surgical implantation as an adjunct to surgical and systemic infection control.
During the period from 1996-2003, there was a 49% rise in the number of new cardiac rhythm medical device (CRM or CRMD implantations but a 310% increase in the number of hospitalizations due to infections related to CRM implants. (2.8 fold increase for pacemakers and 6-fold increase for ICDs). Further, CRM infection increased the risk of in-hospital death more than 2-fold. The challenges faced when treating such implant infections emphasize the critical need to develop improved methods of preventing the infection of implantable devices.
Hence, the incidence of implantable device-related infections continues to pose significant clinical problems, not only with CRMs. but also with other implantable devices such as neurostimulators and infusion pumps are susceptible to infection risks.
The most common bacterial strains involved in the etiology of cardiac device infections include Staphylococcus aureus (S. aureus), and coagulase-negative Staphylococci such as S. epidermidis. Staphylococcal species, including methicillin-resistant S. aureus (MRSA), account for more than ⅔ of cardiac device infections in most published series. These bacteria are able to adhere to device surfaces and in some cases form a biofilm consisting of a polysaccharide matrix surrounding the microorganisms. This matrix protects the microorganisms from antibiotics and host defenses, making the infection highly resistant to antibiotic regimens. Cardiac device infections by these microorganisms most often occur within the generator pocket, and are believed to be due mainly to local contamination at the time of device implantation. Studies have shown that approximately 30% of the patients with pocket infections also had bacteremia. In most cases, whether the patient presents with bacteremia or not, infection of the intravascular portion of the lead is often present, generally caused by progression of the infection from the generator pocket. Due to the ineffectiveness of systemic antibiotics to penetrate through tissue and reach high enough concentrations to eradicate the localized device contamination and pocket infection, as well as the involvement of generator and leads, the prevailing medical opinion is that surgical removal of the generator and leads is the most effective treatment once a pocket infection is diagnosed. This type of surgical treatment is both costly and risky for patients dependent on the device. The estimated cost to treat each infection is $32,000, with total estimated costs of all device-related infections estimated at $640 million per year, excluding the costs of device replacement.
Meta-analysis of prospective randomized trials suggests a consistent protective effect against CRMD infections by using systemic antibiotics pre- and post-implantation. However, while the use of pre- and post-operative systemic antibiotics is proven effective, several studies demonstrate a lack of consistent compliance with standards for preventing surgical site infections. The lack of compliance, along with a desire to reduce the use of systemic antibiotics to minimize the development of resistant organisms, provides significant motivation to develop a more effective means to prevent the initial infection at the time of implant.
Coating antimicrobial agents directly onto implantable medical devices or impregnating such devices with antimicrobial agents can potentially eliminate or reduce the microorganism burden at implant, and has been proposed to provide a device with “long lasting resistance to staphylococcal biofilm colonization” by coating or impregnating rifampin and minocycline, or rifampin and novobiocin, on the surface of an indwelling medical devices (Abstract, U.S. Pat. No. 5,217,493 and generally, U.S. Pat. Nos. 5,624,704 and 5,902,283). In another example, impregnation of central venous catheters with a combination of rifampin and minocyclin has been associated with a reduction of catheter-associated bacteremia. However, these impregnated devices have minimal capacity to elute the antimicrobial agents into the surrounding tissue and little if any ability to deliver it in more than miniscule quantities by virtue of the methodology employed to coat or impregnate the drugs. These limitations may make prevention or reduction of biofilm formation less effective, and may increase the development of resistant strains by eluting such low quantities of drug such that all organisms are not eradicated.
Pocket infection remains one of the most significant problems facing CRM implants, with reports of 2-8% of implants developing infection. Because the infections typically include biofilm formation on the device surface, antibiotics are largely ineffective in eliminating the etiologic microorganisms because, at least in part, the biofilm protects the bacteria residing within the biofilm from destruction. Novel products aimed at preventing not only device colonization but also biofilm formation at the time the pocket is contaminated may provide an important step in reducing device infections.
The present invention demonstrates that a pouch made of biopolymer/polypropylene mesh incorporated with one or more antimicrobial drugs is effective at preventing bacteria from colonizing the device and forming biofilms.
In addition, the present invention addresses these needs (preventing or inhibiting infections) as well as others, such as pain relief and inhibition or reduction of scar tissue, fibrosis and the like, by providing temporarily stiffened meshes formed into pouches or other receptacles to hold an implantable medical device upon implantation.